- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04881214
COVID-19 Pneumonia: Pulmonary Physiology, Health-related Quality of Life and Benefit of a Rehabilitation Program (COVISQAR)
Impact of COVID-19 Pneumonia on Pulmonary Physiology, Health-related Quality of Life and Benefit of a Rehabilitation Program (COVISQAR)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
COVID-19 is an emerging pandemic disease caused by a novel coronavirus (SARS-CoV-2) since December 2019. This condition may be associated with a severe pneumonia and an acute respiratory distress syndrome (ARDS) resulting in a high mortality and morbidity.A standardized follow up of COVID-19 patients after discharge from Geneva University Hospitals (Covicare) was implemented since March 29th 2020 by the divisions of infectious disease and respiratory medicine, in association with the primary care medicine department. A follow-up is ensured until one month after discharge. All patients are registered in a database (REDCapTM,Tennessee, USA).
The pathophysiological mechanisms of ARDS in COVID-19 and its long-term consequences on respiratory and cardiovascular systems remain unclear. Several histopathological studies have demonstrated occurrence of interstitial lung disease. Furthermore, there are some reports of associated endothelitis, thrombosis in the microcirculation5 and a high prevalence of venous thrombo-embolic events in ICU admitted patients, with pulmonary embolism accounting for 85% of those events.Both these changes contribute to increase heterogeneity of ventilation - perfusion ratio (VA/Q), thereby widening the alveolar - arterial oxygen gradient, and thus causing serious hypoxaemia, with remarkable fall of arterial oxygen saturation (SaO2). Finally, the interstitial pneumopathy may cause a persisting reduction of lung diffusing capacity for carbon monoxide (DLCO), further decreasing SaO2 even after recovery from COVID-19 pneumonia.
Chest Dual-Energy Computed Tomography (DECT) enables a combined functional and morphological analysis of the lung in a single and simple acquisition. Because of the attenuation properties of iodine at two different photon energies (80 and 140kV), DECT is able to reveal pulmonary blood volume distribution and generate color-coded pulmonary iodine volume maps, corresponding to the pulmonary perfusion. These pulmonary perfusion maps allow a qualitative analysis of the perfusion.Furthermore, the iodine concentration of the lung confers an objective and quantitative regional analysis of the perfusion. In comparison with a conventional CT, no additional intravenous iodine contrast medium injection or radiation doses are needed; a functional image processing is simply added. We recently demonstrated how DECT may help to define lung perfusion changes after therapeutic measures in patients with chronic obstructive pulmonary disease. Moreover, DECT offers an excellent correlation with perfusion scintigraphy (V/Q scan). DECT also offers a superior anatomic and functional comprehension by simultaneously recording the vascular anatomy, parenchymal morphology, and functional perfusion. Consequently, DECT may provide important information both on persisting parenchymal and perfusion alteration after COVID-19.
In addition to the pulmonary component, the systemic inflammation state due to the concurring "cytokine storm syndrome" may have an important role in the development of neuromuscular alterations, independently of direct consequences of hospitalization in intensive care unit. Neuromuscular alterations concur with lung function impairment in compromising the functional state of the patient. As a consequence, we ought to expect a reduction of physical exercise capacity, which is normally determined by a VO2max measurement during cardiopulmonary exercise test (CPET) and by means of the six-minute walk test (6MWT).
Moreover, it is well described that ARDS is associated with a significant long-term morbidity. At one year, 80% of ARDS survivors have a reduced diffusing capacity and 20% suffer from an airflow obstruction. 35% of patients have an exercise limitation based on the 6MWT at two years. Moreover, impairment in lung function, musculoskeletal dysfunction and functional limitation are linked to health-related quality of life (HRQL) decrement.
Studies from a cohort of patients who suffered from ARDS due to SARS-CoV-1 in 2002 showed a positive correlation between lung function and the HRQL physical functioning domain. Distance performed during 6MWT correlated also with almost all Short Form Health Survey-36 (SF-36) domains. Furthermore, mood disorders are commonly described in ARDS survivors, with studies reporting up to 50% of depression at one year in this population. Depression and anxiety are themselves associated with lower HRQL scores.
Pulmonary rehabilitation has been shown to improve HRQL, maximal exercise capacity and 6MWD in chronic pulmonary disease. It was also shown that 2 months of ambulatory pulmonary rehabilitation improved pulmonary function and the St. George's Respiratory Questionnaire (SGRQ) at 3 and 6 months post-discharge following recovery from ARDS due to severe influenza A (H1N1 in 2009) pneumonitis.
The purpose of this study is 1/ to explore the long-term impact of COVID-19 on physiological respiratory parameters, functional capacity, HRQL and mood disturbances ; 2/ to assess the benefit of a pulmonary rehabilitation program on these outcomes through a randomized-control study, and 3/ to determine the contribution of DECT to the understanding of the pathophysiological alterations in patients with functional sequelae of COVID-19 infection.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Geneva, Switzerland, 1205
- Hopitaux Universitaires de Geneve
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Patients will be eligible for inclusion if they fulfil all the following criteria:
- Patients aged ≥ 18 years.
- Confirmed diagnosis of SARS-Cov-2 infection by nasal swab, other viral sample (i.e. sputum, bronchoalveolar lavage) or Chest imaging suggestive of SARS-CoV-2 pneumonia (Chest X-ray or CT-scan).
- Requirement for oxygen supplementation.
- Persistent respiratory symptoms (i.e. dyspnoea, cough) or asthenia.
- Abnormal 6MWT at 3 months (distance < 90% predicted or desaturation ≥ 3% or Borg >5) and/or abnormal lung function as described by the international recommendations
Patients will be excluded if they:
- Already had existing severe and symptomatic pulmonary condition before COVID-19 pneumonia
- Are unable to execute the different tests and surveys because of cognitive or physical limitations.
- Are already included in a structured rehabilitation program
- Have comorbidities with a life expectancy of less than 12 months.
- Any relevant acute medical disorder/acute disease state judged by the investigators as likely to represent a risk for the patient to fulfil a rehabilitation program or requiring urgent investigations.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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NO_INTERVENTION: Control
Patients in this arm will receive standard of care
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EXPERIMENTAL: Pulmonary Rehabilitation
Patients will undergo a 12-weeks Pulmonary rehabilitation program.
It will include 3 sessions of supervised exercise per week, as initially proposed on COPD patients.
Patients will exercise on electromagnetically braked cycle ergometers for 45 min by alternating 30-s exercise intervals at 100% of peak-work rate estimated during the initial incremental test, with 30-s rest periods.
Total workload will be increased (by 5%) on a weekly basis.
Strength training of lower and upper limbs, will also be included.
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pulmonary rehabilitation for 12 weeks, 3 times a week.
control will take place at 3, 6 and 12 months
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effect of ambulatory pulmonary rehabilitation in health related quality of life
Time Frame: 12 months
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St George's Respiratory questionnaire change (units).
Scores range from 0 to 100, with higher scores indicating more limitations
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12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Long-term consequences of COVID-19 pneumonia on VEMS
Time Frame: 12 months
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Change in VEMS (L, % predicted)
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12 months
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Long-term consequences of COVID-19 pneumonia on Vital Capacity
Time Frame: 12 months
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Change in Vital Capacity (L, % predicted)
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12 months
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Long-term consequences of COVID-19 pneumonia on Total Lung Capacity
Time Frame: 12 months
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Change in Total Lung Capacity (L, % predicted)
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12 months
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Long-term consequences of COVID-19 pneumonia on diffusion capacity of CO
Time Frame: 12 months
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Change in diffusion capacity of CO (ml/min/kPa, % predicted)
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12 months
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long-term consequences of COVID-19 pneumonia on Vital Capacity (VC)
Time Frame: 12 months
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absolute value (liters) measured at inclusion and at the end of the study period with spirometry
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12 months
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long-term consequences of COVID-19 pneumonia on total lung capacity (TLC)
Time Frame: 12 months
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absolute value (liters) measured at inclusion and at the end of the study period with plethysmography
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12 months
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long-term consequences of COVID-19 pneumonia on diffusing capacity for carbon monoxide (DLCO)
Time Frame: 12 months
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absolute value (ml/min/kPa) measured at inclusion and at the end of the study period with plethysmography
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12 months
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Incidence of interstitial lung disease and/or images suggestive of abnormalities in the pulmonary circulation.
Time Frame: 3 months
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Evaluated with a chest dual energy Computed Tomography: presence of honeycombing, bronchiectasis or acute or chronic thromboembolism.
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3 months
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Effect of COVID-19 pneumonia on The Short Form 36 (SF-36) questionnaire score
Time Frame: 12 months
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measured at inclusion and at the end of the study.
Score from 0 (poor health) to 100 (perfect health)
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12 months
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Effect of COVID-19 pneumonia on Hospital Anxiety and Depression Scale (HADS) score
Time Frame: 12 months
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measured at inclusion and at the end of the study. .
Each of them is coded From 0 to 3, with a score varying from 0 to 21
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12 months
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Effect of pulmonary rehabilitation in VO2 max during cardiopulmonary exercise testing (CPET)
Time Frame: 3,6 and 12 months
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Change in VO2 max (ml/min/kg)
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3,6 and 12 months
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Effect of pulmonary rehabilitation in power during cardiopulmonary exercise testing (CPET)
Time Frame: 3,6 and 12 months
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Change in power max (Watts)
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3,6 and 12 months
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Effect of pulmonary rehabilitation in ventilation during cardiopulmonary exercise testing (CPET)
Time Frame: 3,6 and 12 months
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Change in ventilation (L/min)
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3,6 and 12 months
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Effect of pulmonary rehabilitation in Tidal Volume during cardiopulmonary exercise testing (CPET)
Time Frame: 3,6 and 12 months
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Change in Tidal Volume (L)
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3,6 and 12 months
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Effect of pulmonary rehabilitation in 6 minutes walk test distance
Time Frame: 3,6 and 12 months
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Change in meters
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3,6 and 12 months
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Effect of pulmonary rehabilitation in 6 minutes walk test dyspnea
Time Frame: 3,6 and 12 months
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Change in self reported Borg dyspnea
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3,6 and 12 months
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Effect of pulmonary rehabilitation in cardiac output during CPET
Time Frame: 3,6 and 12 months
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ANOVA comparison of cardiac output with 2 non-invasive measurement of cardiac output
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3,6 and 12 months
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Evaluation of COVID-19 impact in pulmonary shunt effect
Time Frame: 2,6 and 12 months
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Change in pulmonary shunt (delta kPa)
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2,6 and 12 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Lador Frédéric, MD-PHD, Hopitaux Universitaires de Geneve
Publications and helpful links
General Publications
- Finegan O, Fonseca S, Guyomarc'h P, Morcillo Mendez MD, Rodriguez Gonzalez J, Tidball-Binz M, Winter KA; ICRC Advisory Group on the Management of COVID-19 Related Fatalities. International Committee of the Red Cross (ICRC): General guidance for the management of the dead related to COVID-19. Forensic Sci Int Synerg. 2020 Mar 31;2:129-137. doi: 10.1016/j.fsisyn.2020.03.007. eCollection 2020.
- Correction to Lancet Respir Med 2020; 8: 420-22. Lancet Respir Med. 2020 Apr;8(4):e26. doi: 10.1016/S2213-2600(20)30085-0. Epub 2020 Feb 25. No abstract available.
- Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer. J Thorac Oncol. 2020 May;15(5):700-704. doi: 10.1016/j.jtho.2020.02.010. Epub 2020 Feb 28.
- Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-1418. doi: 10.1016/S0140-6736(20)30937-5. Epub 2020 Apr 21. No abstract available.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Hypertension
- COVID-19
- Lung Diseases
- Pneumonia
- Hypertension, Pulmonary
Other Study ID Numbers
- 2020-001457
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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